Perini Ilaria, Elia Ilaria, Lo Nigro Antonio, Ronzoni Flavio, Berardi Emanuele, Grosemans Hanne, Fukada So-ichiro, Sampaolesi Maurilio
Translational Cardiomyology Laboratory, Embryo and Stem Cell Biology Unit, Dept of Development and Regeneration, KU Leuven, Belgium.
Translational Cardiomyology Laboratory, Embryo and Stem Cell Biology Unit, Dept of Development and Regeneration, KU Leuven, Belgium; Vesalius Research Center, Belgium and Department of Oncology, VIB, KU Leuven, Belgium.
Biochem Biophys Res Commun. 2015 Aug 28;464(3):755-61. doi: 10.1016/j.bbrc.2015.07.022. Epub 2015 Jul 8.
Met Activating Genetically Improved Chimeric Factor 1 (Magic-F1) is a human recombinant protein, derived from dimerization of the receptor-binding domain of hepatocyte growth factor. Previous experiments demonstrate that in transgenic mice, the skeletal muscle specific expression of Magic-F1 can induce a constitutive muscular hypertrophy, improving running performance and accelerating muscle regeneration after injury. In order to evaluate the therapeutic potential of Magic-F1, we tested its effect on multipotent and pluripotent stem cells. In murine mesoangioblasts (adult vessel-associated stem cells), the presence of Magic-F1 did not alter their osteogenic, adipogenic or smooth muscle differentiation ability. However, when analyzing their myogenic potential, mesoangioblasts expressing Magic-F1 differentiated spontaneously into myotubes. Finally, Magic-F1 inducible cassette was inserted into a murine embryonic stem cell line by homologous recombination. When embryonic stem cells were subjected to myogenic differentiation, the presence of Magic-F1 resulted in the upregulation of Pax3 and Pax7 that enhanced the myogenic commitment of transgenic pluripotent stem cells. Taken together our results candidate Magic-F1 as a potent myogenic stimulator, able to enhance muscular differentiation from both adult and pluripotent stem cells.
甲磺酸激活基因改良嵌合因子1（Magic-F1）是一种重组人蛋白，由肝细胞生长因子的受体结合域二聚化衍生而来。先前的实验表明，在转基因小鼠中，Magic-F1的骨骼肌特异性表达可诱导持续性肌肉肥大，改善跑步性能并加速损伤后的肌肉再生。为了评估Magic-F1的治疗潜力，我们测试了其对多能和全能干细胞的作用。在小鼠中胚层血管母细胞（成体血管相关干细胞）中，Magic-F1的存在并未改变它们的成骨、成脂或平滑肌分化能力。然而，在分析它们的成肌潜力时，表达Magic-F1的中胚层血管母细胞会自发分化为肌管。最后，通过同源重组将Magic-F1诱导盒插入小鼠胚胎干细胞系。当胚胎干细胞进行成肌分化时，Magic-F1的存在导致Pax3和Pax7上调，增强了转基因全能干细胞的成肌定向分化。综合我们的结果，Magic-F1有望成为一种强大的成肌刺激因子，能够增强成体干细胞和全能干细胞的肌肉分化能力。
